Flavoring agent

ABSTRACT

WHEREIN R is hydrogen or a methyl group.   Enhancement of the flavor of foodstuffs is achieved by the addition of an effective flavor-modifying amount of a diphenyl of the formula:

United States Patent 1 1 Winter et al.

Dec. 2, l 975 FLAVORING AGENT Inventors: Max Winter, Geneva; Fritz Gautschi, Vaud; Ivon Flament; Max Stoll, both of Geneva, all of Switzerland; Irving M. Goldman, Niantic, Conn.

Assignee: Firmenich & Cie, Geneva,

Switzerland Filed: June 24, 1974 Appl. No.: 482,821

Related 1.1.5. Application Data US. Cl. 426/538 Int. Cl. A23L 1/226; A23L l/234 Field of Search 426/65, 175, 193, 221,

References Cited OTHER PUBLICATIONS Compt. Rend, 177, 452453, (1923).

Primary ExaminerA. Louis Monacell Assistant Examiner-Esther L. Massung Attorney, Agent, or FirmBruno P. Struzzi; Thomas V. Sullivan; Howard J. Newby [57] ABSTRACT Enhancement of the flavor of foodstuffs is achieved by the addition ofan effective flavor-modifying amount of a diphenyl of the formula:

wherein R is hydrogen or a methyl group.

24 Claims, N0 Drawings FLAVORING AGENT This is a division of application Ser. No. 243,866 filed Apr. 13, 1972, which is a division of application Ser. No. 70,560 filed Sept. 8, I970, now US. Pat. No. 3,702,253; which latter application is a continuation of now-abandoned application Ser. No. 543,069 filed Apr. 18, 1966, which is a continuation-in-part of nowabandoned application Ser. No. 452,342 filed Apr. 30,

1965. The invention relates to flavor agents in general. More particularly the invention relates to chemical compounds or compositions which have been found to have utility in the alteration of flavor or flavor characteristics of substances, whether naturally occurring or synthetic. Still more particularly the invention relates to a group of chemical compounds which have been found to be useful in the area of flavor-note alteration, whether by the enhancement of flavors or flavor-notes that are characteristic in asubstance, by the alteration of a flavor or a flavor-note from a less to a more desirable one, or by the complete or partial masking of a flavor or flavor-note.

As is generally recognized by those familiar with the art,the science of flavor technology is an extremely complex one. Although much is known about flavor and flavor technology there is still a great deal to be learned in the field and the body of scientific literature is being rapidly expanded by those working in the area. The technology of flavor synthesis and blending of various flavor elements to achieve certain desirable results is of great commercial importance at the present stage of industrial advance. Commercial production of consumer goods from synthetic starting'materials is becoming more and more common, and desirable, as world population continues to increase its demands upon the finite capacity for the production of natural products. Industry is also continually seeking means of upgrading natural products methods of altering or enhancing the qualities of taste of less desirable natural products usually more "abundant into more desirable product qualities. Often, for example, a product can be made commercially attractive only by masking or blanking out an undesirable flavorcomponent. Formerly, before the advent of the flavor chemist and his technology, this unit of production would have been lost, or atleast, would have had to have been re-processed to a useable quality. By the use of specifically designed flavoring agents, however, the undesirable flavor note can be eliminated or masked with another desirable one, and the expensive and time-consuming reprocessing step eliminatedor the production batch saved for use. Too, it is common in some segments of the industry, particularly the food industry, to add flavor agents to production units to enhance or bring out a desirable flavor characteristics of products and by so doing to render the product more desirable from a consumer preference standpoint.

It is the object of this. invention therefore, to provide the flavor technologist with additional tools for his use in the alteration of food flavors, whether it be flavor or flavor-note alteration generally or the enhancement or improvement of flavor or flavor notes specifically.

It is a further object of the invention to fumish a group of chemical compositions which have utility in the technology of flavor alteration, whether added to solid or liquid compositions for human consumption, and which may be used in either solid or liquid form.

A further object of the invention is to describe several groups of chemical compounds having desirable utility as flavor agents which may be prepared synthetically, thus enabling the food technologist to alter or enhance' his product without drawing upon a natural product for the flavor agent.

A still further object of the invention is to describe a group of chemical compounds capable of synthesis from readily available organic substances which may be used singly or in combination to alter the flavor or flavor notes of compositions for food use, whether used in micro-quantities such as parts-per-million or in larger quantities, as the dictates of the end results may require.

Other objects will become apparent to those skilled in the art as the description proceeds.

Thus, in accordance with the concept of the instant invention, there is set out below a series of groups of compounds which have been found to have utility as flavor agents and to represent valuable materials to the food technologist who wishes to alter the flavor components of foods or food products either liquid foods or beverages, such as fruit and vegetable juices, milk, coffee, tea, cocoa, chocolate, and the like or solid foods such as cereals, flours, confections, vegetables, meats, etc. The flavor agents may be used either in liquid or solid form and are used in quantities designed to give the desired results, as will be more clearly explained as the description proceeds. i

The chemical compounds which have been found to have utility as flavor agents may be generally classified according to the following groups:

I. Diphenyls II. Substituted Naphthalenes 4 III. Furan Hydrocarbons IV. Thiophene Hydrocarbons V. Pyrrole Hydrocarbons VI. Pyridine Hydrocarbons VII. Pyrazine Hydrocarbons VIII. Aliphatic and Aromatic Alcohols IX. Furan Ethers X. Thiophene Ethers XI. Thiazole Alcohols XII. Pyridine Ethers and Alcohols XIII. Pyraz ine Ethers and Alcohols XIV. Benzofuran Carbonyl Compounds XV. Thiophene Aldehydes XVI. Pyrrole Aldehydes XVII. Pyrazine Carbonyl Compounds XVIII. Aliphatic and Aromatic Ketones XIX. Furan Ketones XX. Thiophene Ketones XXI. Pyrrole Ketones XXII. Thiazole Carbonyl Compounds XXIII. Pyridine Carbonyl Compounds XXIV. a-Diketones XXV. Thiophene-a-diketones XXVI. Pyrrol-a-diketones XXVII. Furan Esters XXVIII. Thiophene Esters XXIX. Pyridine Esters XXX. Aromatic Sulfur Compounds XXXI. Furan Sulfur Compounds XXXII. Thiophene Sulfur Compounds XXXIII. Pyridine Sulfur Compounds XXXIV. Pyrrole Sulfur Compounds XXV. Pyrazine Sulfur Compounds XXXVI. Phenols and Phenol Ethers XXXVII. Aliphatic Oxoalcohols XXXVIII. Miscellaneous The above groupings are selected more for reasons of chemical similarity than because of flavor alteration characteristics as will be more specifically described in relation to the more complete definition afforded each particular group.

3 The flavor agents or flavor modifying compositions of this invention are available to the food technologists in a variety of forms. It is usually preferable to use the agents in the form of a solution, for ease of dilution, exactitude of measurement, efficiency of distribution in the end use, etc. However the chemical nature of the compound, its solubility in acceptable solvents, its stability, and other characteristics may dictate the form in which it is used.

The amounts of the agents used is also subject to wide variation, of course. More concentrated materials, and those with the greatest degree of flavor modifying ability will be used in lesser amounts. Some degree of experimentation is, of course, required to achieve the desired results. A small, but flavor modifying amount, of the agents is blended with the material whose total flavor is to be altered, the amount depending upon the end result desired.

Two different types of methods were used in testing the compounds listed in this specification for their utility as flavor agents, flavor modifiers, flavor alteration agents, flavor-note enhancers, and the like. The first type method (A) served the purpose of determining the intrinsic taste, flavor and aroma of each individual compound. The second type methods (B) and (C) were used for testing the flavorand aroma-modifying or -enhancing effects of the compounds hereinafter listed on coffee products and more particularly on spray-dried soluble coffee products commercially known as instant coffee.

METHOD A The vehicle used for testing the flavor compounds was a 65 percent solution of cane sugar in tap water. The flavor compounds were incorporated in this sugar syrup in the form of 1 percent or 1 per 1,000 by weight solutions in 96 percent ethyl alcohol, The concentration of the flavor compounds in the sugar syrup varied between about 0.005 and 5 g. for 100 liters of syrup according to the varying strength of flavor compounds. Samples of each flavored sugar syrup were submitted to the members of the tasting panels. After tasting the samples each member had to give an evaluation of each flavor compound in terms of descriptive words.

In the evaluation of materials for the alteration or enhancement of coffee flavor or of coffee flavor notes it is essential that the equipment used, coffee pots, cups, spoons, measuring equipment, etc. by absolutely clean prior to use.

METHOD B The coffee base was prepared by dissolving l g. of a commercial spray-dried soluble coffee in boiling water. A sufiicient number of pots was prepared to provide one pot for each flavor agent to be evaluated plus one control. The flavor agent was added to the coffee base in the form of a 1 percent or 1 per 1000 by weight alcoholic solution at concentrations varying between 0.005 and 5 g. of flavor agent for 100 liters of coffee base. The measured quantity of the flavor agent was added to a pot of the coffee base material, stirred well, and poured immediately into cups for the organoleptic evaluation. The taste tests were made within a short time (not more than 15 minutes) after the final composition to be tested was prepared.

The organoleptic evaluation involved grading a series of cups that were coded, the taster merely rating the coded cups against the standard or control which did 4 not contain the flavor agent. The standard was placed at the first position in a series of cups. The tasters were asked to ascertain whether or not there existed differences in the flavor of the samples to be tested as compared with the control. The tasters were furthermore asked to describe and characterize the various flavor notes and types determined.

METHOD C Using boiling Crystal Spring Water, to provide a clean starting taste, a 1.35 percent solution of relatively bland tasting commercially available spray-dried soluble coffee was prepared. The containers used preferably the lower portion of a glass coffee maker was absolutely clean, as was the other equipment used, eg cups and spoons.

A sufficient number of containers, or pots, were used to accomodate each flavor fraction to be studied, plus one control. The flavor fraction was measured carefully with a micro-syringe, adding from 2 to microliters of the flavor fraction per pot. The mixture of coffee solution and flavor fraction was stirred and immediately poured into cups for tasting. At least 5 experienced tasters are used. The tasting should begin at least within 15 minutes after the solution is prepared. If not, the solution should be discarded and fresh solution prepared.

The cups are coded and the samples are not identified. A standard sample is included in which no flavor fraction has been added- The taster is asked to identify and describe the flavor enhancement or modification noted. '7

In the following specific description of the com pounds of the Groups listed above (I XXXVIII) there is first given the structural formula followed by a list of members of the group which have been found to have outstanding utility in the concept of this invention. Immediately following the chemical name of each member there is given the commercial source or a literature reference giving a method for its preparation. Commercially available products will be identified by the abbreviation c.a., and may be obtained from FLUKA, A.G., Buchs S.G., Switzerland; ALDRICH CHEM. CO., Milwaukee, Wis.; DR.F. RASCI-IIG GMBH, Ludwigshafen a. Rh., West-Germany; or K & K LABORATORIES INC., Plainview, NY. 11803.

In those instances wherein new compounds are described a detailed method of preparation is given following the list of the group members. New compounds will be identified by the abbreviation n.c.

The results of the organoleptic evaluation tests are set out in the group of TABLES following the detailed description of the groups of compounds.

I. Diphenyls In this first group of compounds are included those having the structural formula:

( cl. diphenyl b. Z-methyl-diphenyl c. 3-methyl-diphenyl d. 4-methyl-diphenyl e. 4,4'-dimethyl-diphenyl A Organoleptic evaluations as flavor agents are described in TABLE I below.

11. Substituted Naphthalenes the carbon atoms of the substituent groups does not exceed 3; and compounds of the formula:

(3) I I Compounds in this group are those having the gen- 5 l l eral formula: 1 0 2 R n wherein R is hydrogen or a methyl group and wherein R is a l I R --Cll ko R wherein R is hydrogen or an alkyl group, e.g. methyl or ethyl, at least one of the Rs being an alkyl group.

Typical compounds include:

( l) a. alpha-methyl-naphthalene c.a. b. beta-methyl-naphthalene c.a. c. beta-ethyl-naphthalene c.a. d. 1,2-dimethyl-naphthalene c a R being hydrogen or a methyl group such that R an e. 1,3-dimethyl-naphthalene c.a. R are not both hydrogen. 1 f. 1,4-dimethyl-naphthalene c.a. g. hmimemylmapmhalene CA Spec1fic compounds included in this group of com h. Lfi-dimethylmaphthalene c.a. Pounds are:

Bull. 1947. 453 C.A. 1961. 859058 (1) a. 2-vinyl-furan b. 2-(1)-pentenyl-furan (2) a. benzofuran c. Z-ethyl-benzofuran J.A.C.S. 73,754 (1951) d. 2,3-dimethyl-benzofuran Soc. 1955, 3689 e. 2-vinyl-benzofuran J.A.C.S. 73, 754 (1951) f. 2-isopropenyl-benzofuran n.c. g. 7-methyl-benzofuran J.Chem.Soc. 1920. 1534 h. 7-ethyl-benzofuran n.c. i. 2,7-dimethylbenzofuran n.c. (3) a. 2,2'-difuryl J.A.C.S. 73, 1271 (1951) I b. 5-methyl-2,2-difuryl-methane C.A. 1957, 6594a c. 5 ,5 '-dimethyl-2,2 '-difuryl-methane Holv. 1932, 1068 %.2-gi :y:- i The new compounds included in Group 111 can be imet y-nap aene c.a. k. l,3,7-trimethyl-naphthalene prepared by the methods described below. (2) f. 2-Iso- 1. 2.3,S-trimethyl-naphthalene c.a. propenyl-benzofuran According to the method de- 2-3,fi-mmethyl-navhthalene scribed in J.A.C.S. 73, 754 1951 2-acetyl-benzofuran n. alpha-ethyl-naphthalene c.a. o. 1,7-dimethyl-naphthalene c.a. 1S reacted with methyl-magnesium bromide to form 2- P Lidimflhylmaphthalene (Z-hydroxyisopropyl)-benzofuran which is converted to its acetate. Pyrolysis of the acetate yields 2-isopropenyl-benzofuran of b.p. 8l839C./0.001 mm. Hg.

(2) h. 7-Ethyl-benzofur'an is prepared by the method described in J.Chem.Soc. 1920, 1534, but using 0- ethylphenolinate of o-cresol. The MS. of the product Furan Hydrocarbons thus obtained shows the following ion peaks with the The compounds of this group which have utility a relative intensities given within brackets: 131 (100 percording to the inventive concept are selected from the 146 P and 77 P class of compounds having the general formula: y nz u an ethyl-ben20furan (of. compound (2) g.) is subjected to a WILSMEYER reaction to form 7-methyl-benzofuran-2-aldehyde (l) I l which is converted into 2,7-dimethyl-benzofuran by a WOLFF-KISHNER reaction by the method described 0 in Bull.Soc.Chim.France 29, 1875 (1952). The product thus obtained has the following peaks in its MS: 146 (100%), 145 (92 percent) and 131 (32 percent).

Organoleptic evaluations of this group of compounds are set out in TABLE III below.

The compounds enumerated above were evaluated organoleptically and gave the results set out in TABLE 45 11 below.

wherein R is hydrogen or an alkyl group containing from 1 to 3 carbon atoms; compounds of the formula:

IV. Thiophene Hydrocarbons n The thiophene hydrocarbons having utility in accor- (2) R dance with the instant inventive concept are those R o compounds described by the structural formula:

wherein R is hydrogen or an alkyl or an alkenyl group (1) of from 1 to 3 carbon atoms, provided that the sum of 7 8 wherein R and R are hydrogen, methyl, ethyl, vinyl or V. Pyrrole Hydrocarbons P PY Compounds of this group have the general formulae:

the compound of the formula:

3 5 [I ll N wherein R is alkyl, e.g. ethyl, amyl, isoamyl, or alphamethylbutyl, and

the compounds of the formula: I

U j s. 3) an n 2 2 t 2 X 1 x wherein X is oxygen or sulfur and R is hydrogen or a wherein R and R are hydrogen or methyl groups, and methyl group, provided that, if X represents oxygen, R

wherein X is oxygen or sulfur; the compounds of the is methyl. formula Typical compounds of this group include:

(l) a. l-ethyl-pyrrole Helv. 10, 387 (1927) b. l-n-amyl-pyrrole Helv. 10, 387 (1927) c. l-isoamyl-pyrrole Helv. 10, 387 (1927) d. l-(alphamethyl-butyl)-pyrrole Helv. 10, 387 (1927) (2) a. l-(5-methyl-2-furfuryl)-pyrrole n.c.', b.p. l04C./1l mm;

prepared by the same method as (l)a, b. l-thienyl-pyrrole J.Org.Chem. 28,574 (I965) r Organoleptic test evaluations are set out in TABLE V I l a below.

R 3 a x 2 VI Pyridine Hydrocarbons The compounds of this group which have utility acwherein R and R are hydrogen or methyl groups, and cording to the instant concept are to be described as the compounds of the formula falling under the general formula:

(5) R R (1) R R 1 N wherein R and R represent hydrogen or alkyl groups.

Typical compounds of this class of compounds are: wherein R R and R are hydrogen, alkyl, e.g. methyl,

(l) a. Z-methyl-thiophene c.a. b. B-methyI-thiophene c.a. c. Z-ethyhthiophene c.a. d. B-ethyl-thiophene Bull. I955, 424 e. 2-propyl-thiophene J.A.C.S. 70, 391, Bull.

1955, 361 f. Z-vinyl-thiophene Bull. 1955, 424 g. 3-vinyl-thiophene Bull. I955, 424 h. 2-methyl-4-ethyl-thiophene J.A.C.S. 75, 989 (1953) i. Z-methyl5-ethyl-thiophene J.A.C.S. 75, 989 (l953) j. 2-methyl-5'propyl-thiophene J.A.C.S. 75, 989 (1953). k. 2,5-dimethyl-thiophene c.a. (2) a. 2,3,3'.2-thiophenothiophene Soc. 1953, 1837 (3) a. 2,2'-dithienyl-methane .I.A.C.S. 73, I270 (i) b. 5,5'-dimethyl-2,2-dithienyl-methane J.A.C.S. 73, 1270 (1951) c. Z-furyl2-thienyl-mcthane C.A. 57, 9776r (l962) d. (S-methyl-Z-thienyl)-2-furyl-methane CA. 57, 9776r (1962) (4) a. 2,2-dithienyl .|.A.C.S. 78, I958 (1956) b 5,5'dimethyl'2,2-dithienyl-methane J.A.C.S. 78. I958 (1956) (5) a. benzothiophene c.a.

b. Z-methyl-benzothiophene J.A.C.S. 74, 664 (1959) Organoleptic evaluations of these compounds are set ethyl, isobutyl; alkenyl groups, e.g. vinyl, propenyl; aryl out in TABLE IV below. groups; or aralkyl groups; provided that the symbols R R and R are not all hydrogen.

Typical compounds include:

(I 2-methyl-pyridine 3-meth yl-pyridine 3-ethyl-pyridine 2-allyl-pyridine 4-isobutyl-pyridine 2'( l )-propenyl-pyridine 4-( l )-propenyl-pyridine Z-methyl-S-ethyl-pyridine 2,4-dim ethyl-pyridine This important group of compounds have been found to have exceptional utility as flavor agents in accordance with the instant inventive concept. Compounds 25 2,5-dimethylpyridine 2,6-dimethyl-pyridine 3,4-dimethyl-pyridine 3,5-dimethyl-pyridine Z-vinyl-pyridine 4-methyl-pyridine 2-methyl-6-vinyl-pyridine 4-phenyl-pyridine s. 4-benzyl-pyridine t. 2-benzyl-pyridine u. Z-meIhyI-S-ethyl-pyridine g. h. i. 2, dimethyl-pyridlne k. l.

p. q. I.

Organoleptic evaulations are set out in TABLE VI c.a. Bull. 420, (1955) Bull. 420, (l955) Ann. 247, l (1888) Ann. 247, l (1888) VII Pyrazine Hydrocarbons of the group have the general formulae:

N (1) i i l wherein R is hydrogen, alkyl, l-pyrrolyl or 2-thienyl;

and R is alkyl or alkenyl.

below.

i .10 wherein R R and R are alkyl groups having from 1 to 5. carbon atoms,

wherein R R and R are hydrogen or methyl groups,

no 0.0 o-

wherein R and R are alkyl groups containing from 1 to 3 carbon atoms,

.N n (5) 1 I t. 1

wherein R R R and R are alkyl groups containing from 1 to 6 carbon atoms, and

wherein R is methyl or ethyl and R is alkyl or alkenyl with C tOC Compounds of this I group which are of special interest include:

l. 2-methyl-3-(thienyl-2)-pyrazine m 2-ethyl pyrazine n.c. J.Org.Chem. 26, 3379 (1961) n. 2-propyl-pyrazine J.Org.Chem. 26, 3379 t V r .(1961) 0. 2-isopropyl-pyrazine J.0rg.Chem. 26. 3379 (l96l) p. 2-vinyl-pyrazine J.Org.Chem. 26, 3379 (1961) q. Z-isopropenyl-pyrazine n.c.

r. 2-methyl-3-vinyl-pyrazine a. trimethyl-pyrazine 2,3-diethyl-5-methyl-pyrazine S-methyl-quinoxaline Z-methyl-quinoxaline o-methyl quinoxaline 2,3-dimethyl-quinoxaline 2-methyl-3-ethyl-quinoxaline 2,3-diethyl-quinoxaline n.c. J.A.C.S. 72, 844(1950) b. 2,6-dimethyl-3-ethyl-pyrazine n.c. c. 2,S-dimethyl-Ii-ethyl-pyrazine n.c. d; 2,5-dimethyl-3-propyl-pyrazine n.c. c. 2,6-cliethyl-3-methyl-pyrazine n.c. f. 2,5-diethyl-3-methyl pyrazine n.c. g. 2.5-dimethyl-3-butyl-pyrazine n.c.

h. 2,3-dimethyl-5-isoamyl-pyrazine n.c. i. 2,5-dimethyl-3-isoamylrpyrazine n.c.

n.c. Ann. 237. 336 I887) Org.Synth. I30, 86 (1950) Ann. 237. 336 (1887) Ber. 40, 4858 (l907) Ber. 22, S26 (1889) J.A.C.S. 79. 1712 (1957) -continued g. 2-methyl-3-propyl-quinoxaline h. 2-methyl-3-isopropyl-quinoxaline i. Z-methyl-3 butyl-quinoxaline j. 2-methyl-3-isobutyl-quinoxaline k. 2-methyl-3-amyl-quinoxaline l. Z-ethyl-quinoxaline J.Chem.Soc. 1946, 54 J.Chem.Soc. I953. 2822 n.c. J.Chem.Soc. 1943, 322 J.Chem.Soc. l953 2822 Organoleptic evaluations are set out in TABLE Vll below The new compounds of this Group VII can be prepared as follows:

The 2,3-disubstituted pyrazines (formula (1)) can be obtained by a method comprising catalytically dehydrogenating with copper chromite the correspondingly substituted dihydropyrazines which, in turn, can be prepared by condensation of ethylene diamine with the corresponding alpha-diketones. By way of illustration the preparation of 2-methyl-3-ethyl-pyrazine is described in more details.

(l) a. 2-Methyl-3-ethyl-pyrazine. In a 3-necked flask equipped with a stirrer, means for cooling and a dropping funnel there was placed 150 g. of ethylene diamine in 500 ml. ether. After cooling to C there was slowly added with stirring a solution of 250 g. of ethyl methyl diketone in 500 ml. of ether. After the addition was complete, the temperature was allowed to rise to room temperature and the mixture was heated on a water bath for a few minutes. The material separated into 2 phases and the water phase was discarded. The ether phase was dried with sodium sulfate, the solvent was removed by evaporation and the residue distilled under reduced pressure and an inert atmosphere. There was obtained 192 g. of the dihydropyrazine (62 percent yield), boiling point 6l-65C./ll mm. Hg.

In an apparatus similar to that described by Bouveault in Bull IV, 3, 119 (1908) the dihydro pyrazine was distilled under reduced pressure under nitrogen atmosphere through a column containing copper chromite (Girdler 6-13). The catalyst was heated to 300C electrically and the effluent was passed through a Widmer column to separate the unhydrogenated material.

The product was condensed, dried and redistilled; a 90 percent yield was obtained of a product boiling at 57C./l0 mm.Hg.

n Organoleptic evaluations are set out in TABLE VI] belo The same method as used for compound (1) a. was applied for the preparation of the following compounds:

b. 2-methyl-3-isobutyl-pyrazine b.p

c. 2-methyl-3-propyl-pyrazine b.p. 7l-72/l0 mm. Hg. d. Z-methyl-3-isopropyl-pyrazine b.p. 59/l0 mm. Hg.

e. 2-methyl-3-butyl-pyrazine b.p. 83-84/9 mm. Hg.

f. 2-methyl-3-amyl-pyrazine b.p. 98/l0 mm. Hg.

g. 2-methyl-3-hexyl-pyrazine b.p. ll3l l5l9 mm. Hg. i. 2,3-diethyl-pyrazine b.p. 697l/l2 mm. Hg.

(1) j. 2-Ethyl-3-vinyl-pyrazine can be prepared from 2-ethyl-3 methyl-pyrazine by the method described in J.Org.Chem. 27, 1363 (1962). B.p. -80C./l0 mm.Hg.

(l) k. 2-Methyl-3(5,6 )-(pyrrolyl-l)-pyrazine can be prepared as follows: N-Pyrrolyl-lithium is prepared by reacting 0.242 mole (15.4 g.) of butyllithium (as 15 percent suspension in hexane) with 0.22 mole (14.7 g.) of .pyrrole at -20C. in the presence of 100 ml. of tetrahydrofuran. There is then added at room temperature a solution of 0.2 mole (25 .6 g.) of 3(5,6)-chloro-2-methyl-pyrazine [obtained by the method described in J.'Org.Chem. 26, 2356 1961)] in 75 ml. of tetrahydrofuran. The reaction mixture is refluxed for 5 days and subjected to the usual treatments for purifying and isolating the reaction product which is then distilled. There is thus obtained 2-methyl-3(5,6)-N-pyrrolylpyrazine as a fraction distilling at l20l 24C.] 10 Torr.

l) l. 2-(Thienyl-2)-3-methyl-pyrazine is prepared as follows. A solution of 0.36 g. (0.006 mole) of ethylene diamine in 3 ml. of ether is cooled to 0C. To this solution there is added slowly in a nitrogen atmosphere a solution of 0.94 g. (0.006 mole) of (thienyl-2) methyl diketone (obtained by oxidation of 2-propionylthiophene with selenium dioxide) in 3 ml. of absolute ether. The ether is gradually replaced by benzene, and water is removed as an azeotropic mixture with the latter solvent. The reaction product is fractionally distilled, and the fraction boiling at l05C./0.003 mm. Hg. is redistilled through a copper chromite column (GIR- DLER G-l3) heated at 350C. There is thus obtained 2-(thienyl-2)-3-methyl-pyrazine of b.p. 94C./0.03 mm. Hg.

(1) q. 2-lsopropenyl-pyrazine is obtained from 2- ethylpyrazine by the method described in J. Org. Chem. 27, 1363 (1962). It has the following peaks in 13 the MS: 119 (100 percent), 120 (81 percent) and 67 (21 percent).

(1) r. 2-Methyl-3-vinyl-pyrazine is prepared from 2,3-diethylpyrazine by the same method as used for compound (1) q. It has a b.p. of 6667C./13 mm. Hg.

(2) b. 2,6-Dimethyl-3-ethyl-pyrazine is prepared by the addition of an ethyl group at the 3-position of 2,6- dimethylpyrazine by the alkyl-lithium method described by Klein et al. in J.A.C.S. 73, 2949 (1951). The resulting product has a b.p. of 6466C./8 mm. Hg.

(2) c. 2,5-Dimethyl-3-ethyl-pyrazine is prepared by the addition of an ethyl group at the 3-position of 2,5- dimethyl-pyrazine by the alkyl-lithium method described by Klein et al. (loc.cit.). The resulting product has a b.p. of 63-68C./8 mm. Hg.

(2) d. 2,5-Dimethyl-3-propyl-pyrazine is prepared by the addition of an n-propyl group at the 3-position of 2,5-dimethylpyrazine by the alkyl-lithium method described by Klein et al. (loc.cit.). The product is identified by mass spectrometry. It has a b.p. of 80C./1() mm. Hg.

(2) e. 2,6-Diethyl-3-methyl-pyrazine is prepared by the introduction of a methyl group into the 3-position of 2,6-diethylpyrazine by the method of Klein et al. (loc.cit.). The product has a b.p. of 9192C./13 mm. Hg.

(2) f. 2,5-Diethyl-3-methyl-pyrazine is prepared by the introduction of a methyl group into the 3-position of 2,5-diethylpyrazine by the method of Klein et a1. (loc.cit.). The product was isolated by gas chromatography and was identified by mass spectrometry.

(2) g. 2,5-Dimethyl-3-butyl-pyrazine is prepared by introducing a butyl group into the 3-position of 2,5- dimethylpyrazine by the method of Klein et al. (loc.- cit.). The resulting product has a b.p. of 91C./9 mm.

(2) h. 2,3-Dimethyl--isoamyl-pyrazine is prepared by introducing an isoamyl group into the 5-position of 2,3-dimethylpyrazine by the method of Klein et a1. (loc.cit.). The product is identified by mass spectrometry.

(2) i. 2,5-Dimethyl-3-isoamyl-pyrazine is prepared by introducing an isoamyl group into the 3-position of 2,5-dimethylpyrazine by the method of Klein et al. (loc.cit.). The product has a b.p. of 1 l0-120C./l3 mm. Hg.

(2) j. 2,3-Diethyl-S-methyl-pyrazine is prepared by the method described for the preparation of compound (1) a. in Group Vll, using 1,2-diamino-propane instead of ethylene diamine and dipropionyl as the a-diketone. The product has a b.p. of 79-80C./ 12 mm.Hg.

(3) i. 2-Methyl-3-butyl-quinoxaline is obtained by the same method as compound (3) d. of Group VII. It

has a b.p. of l53C./9 mm. Hg.

(3) j. 2-Methyl-3-isobutyl-quinoxaline is obtained by the same method as compound (3) e. of Group VII. It has a m.p. of 9495C.

(4) a. 2-Methyl-6-ethyl-pyrazine was obtained by the alkylation of 2,6-dimethyl-pyrazine by the method described by Levine and Behun in J. Org. Chem. 26, 3379 (1961). It has a boiling point of 5457C./1 1 mm. Hg.

(4) c. 2,6-Diethyl-pyrazine was obtained by subjecting compound (4) a. to a second alkylation by the procedure described above. It has a boiling point of 70 at mm. Hg.

(4) d. 2-Methyl-6-vinyl-pyrazine is obtained by starting with 2,6-dimethyl-pyrazine and following the 14 method of Levine et al. reported in J. Org. Chem. 27, 1363 (1962). It has a b.p. of 74-75/22 mm. Hg.

(5) a. 2,3,5-Trimethyl-6-butyl-pyrazine was prepared by introducing a butyl group into the 6-position of 2,3,5-trimethylpyrazine by the method of Klein et al. (loc.cit.). The product was isolated by gas chromatography and identified by mass spectrometry.

(5) b. 2,3,5-Trimethyl-6-isoamyl-pyrazine was prepared by introducing an isoamyl group into the 6-position of 2,3,5-trimethyl-pyrazine by the method of Klein et al. (loc.cit.). The product had a b.p. of C./10 mm.Hg.

(5) c. 2,5-Dimethyl-3,6-dipropyl-pyrazine was prepared by first forming 3-oximino-2-hexanone by reacting 2-hexanone with nitrosyl chloride according to the method of BOUVEAULT, Bull. [3] 31, 1163 (1904). The autocondensation of two molecules of the iminoketone in the presence of zinc and acetic acid [according to the method described in Chimia 1 1, 310 1957)] yielded 2,5-dimethyl-3,6-dipropyl-pyrazine which had a b.p. of 109l 10C./1O mm. Hg.

(5) d. 2,5-Dimethyl3,6-diisopropyl-pyrazine was prepared by first forming 4-methyl-3-oximino-2-pentanone by reacting 4-methyl-2-pentanone with nitrosyl chloride according to the method of BOUVEAULT, Bull. [3] 31,1163 (1904). The autocondensation of two moles of the imino-ketone in the presence of zinc and acetic acid [according to the method described in Chimia 1 1, 310 (1957)] yielded 2,5-Dimethyl-3,6- diisopropyl-pyrazine which had a b.p. of 91C./8 mm. Hg.

(5) e. 2,5-Dimethyl-3,6-dibutyl-pyrazine was prepared by first forming 3-oximino-2-heptanone by reacting 2-heptanone with nitrosyl chloride according to the method of BOUVEAULT, Bull. [3] 31, 1163 (1904). The autocondensation of two moles of the iminoketone in the presence of zinc and acetic acid [according to the method described in Chimia 1 1, 310 1957)] yielded 2,5-dimethy1-3,6-dibutyl-pyrazine which had a b.p. of 18C./0.002 mm. Hg.

(5) f. 2,5-Dimethyl-3,6-diisobutyl-pyrazine was prepared by first forming 5-methyl-3-oximino-2-hexanone by reacting 5-methyl-2-hexanone with nitrosyl chloride according to the method of BOUVEAULT (loc.cit.). The autocondensation of two moles of the iminoketone in the presence of zinc and acetic acid [according to the method described in Chimia 1 l, 310 (1957)] yielded 2,5-dimethyl-3,6-diisobutyl-pyrazine which had a b.p. of 6970C./0.01 mm. Hg.

(5) g. 2,5-Dimethyl-3,6-diamyl-pyrazine was prepared by first forming 3-oximino-2-octanone by reacting 2-octanone with nitrosyl chloride according to the method of BOUVEAULT (loc.cit.). The autocondensation of two moles of the imino-ketone in the presence of zinc and acetic acid [according to the method described in Chimia 11, 310 (1957)] yielded 2,5-dimethyl-3,6-diamyl-pyrazine which had a b.p. of 78C./0.03 mm. Hg.

(5) h. 2,5-Dimethyl-3,6-dihexyl-pyrazine was prepared by first forming 3-oximino-2-nonanone by reacting 2-nonanone with nitrosyl chloride according to the method of BOUVEAULT (loc.cit.). The autocondensation of two moles of the imino-ketone in the presence of zinc and acetic acid [according to the method described in Chimia 1 1, 310 (1957)] yielded 2,5-dimethyl-3,6-dihexyl-pyrazine which had a b.p. of 112120C./0.01 mm. Hg.

i. 2,3,5-Trimethyl-6-hexyl-pyrazine was prepared by introducing a hexyl group into the 6-position of 2,3,5-trimethylpyrazine by the method of Klein et al. (loc.cit.). The product had a b.p. of 89-9 lC./0.2 mm. Hg.

(5) j. 2,5-Dimethyl-3,6-diethyl-pyrazine is prepared by alkylation of 2,5-dimethyl-3-ethyl-pyrazine according to the alkyl-lithium method described by Klein et a1. [.I.A.C.S. 73, 2949 (1951)]. It has a b.p. of 83-85C./8 mm. Hg.

(6) a. 2-Ethyl-S-methyl-pyrazine was prepared by alkylation of 2,5-dimethyl-pyrazine following the procedure of Levine and Behun described in J. Org. Chem. 26, 3379 (1961). It has a boiling point of 60C./1l mm. Hg.

(6) b. 2-Isopropyl-5-methyl-pyrazine was produced in the preparation of compound (6) a. as a by-product and was separated from the reaction mixture by gas chromatography. Identification was confirmed by mass spectrometry.

(6) c. 2,5-Diethyl-pyrazine was obtained by subjecting compound (6) a. to a second alkylation by the procedure given for compound (6) a. above. It boils at 64C. at 12 mm. Hg.

(6) d. 2-Methyl-5-vinyl-pyrazine was prepared by the method of Levine et al. described at J. Org. Chem. 27, 1363 (1962), starting from 2,5-dimethyl-pyrazine. It has a boiling point of 6566C./l2 mm. Hg.

VIII Aliphatic and Aromatic Alcohols This group comprises compounds having the general formula:

wherein (I) a. n-amylalcohol b. isoamylalcohol c. n-hexanol d. n-heptanol e. n-octanol f. n-nonanol g. n-decanol h. Z-heptanol i. 3-octanol a. phenylethan l-ol b. phenylpropan-l-ol c. cinnamyl alcohol d. phenyl methyl carbinol e. benzyl methyl carbinol f. benzyl ethyl carbinol g. benzyl butyl carbinol h. benzyl amyl carbinol -continued i. benzyl isoamyl curbinol j. benzyl hexyl curbinol n.c.

'benzyl butyl carbinol of b.p. 8891C./0.06 Torr; df

The same method is used for preparing:

(2) h. Benzyl amyl carbinol, b.p. 8lC./0.0l Torr.

(2) i. Benzyl isoamyl carbinol, b.p. 142l43C./13 Torr; df 0.9377; n 1.5009.

(2) j. Benzyl hexyl carbinol, b.p. C./0.01 Torr; d 0.9339; n 1.4997.

Organoleptic evaluation data are listed in TABLE VIII below.

IX. Furan Ethers The compounds of this group have the general formula:

RI/UJHJIRZ wherein R and R are hydrogen; alkyl, e.g. methyl, ethyl; aryl, e.g. phenyl, alkylphenyl; furfuryl, or alkylfurfuryl groups.

Compounds representative of this group include the following:

Ber. 56, 1004 (1923) Ber. 56. 1004 (1923) Bull. 1938, 1151 a. furfuryl methyl ether b. furfuryl ethyl ether c. furfuryl phenyl ether (1. S-methyl-furfuryl furfuryl ether n.c. difurfuryl ether Am. Soc. 49, 1066 (1927) (1) d. S-MethyI-furfuryl ether was prepared by the procedure described by J. E. Zanetti in .I. Am. Chem. Soc. 49, 1066 (1927) for the difurfuryl ether, starting with S-methylfurfuryl bromide (Compt. Rend. 222, 1441 (1946)) instead of furfuryl bromide of Zanetti. The product was isolated by ether extraction of the crude mixture after having diluted with water. For purification the ether extract was distilled twice b.p. 6870C. at 0.01 mm./I-Ig'vacuum. The product was a viscous colourless liquid, darkening rapidly on contact with air.

Organoleptic evaluations are tabulated in TABLE IX.

X Thiophene Ethers This group of compounds are described by the structural formula:

l CHQOR .A.C.S. 49, 1066 (1927) .A.C.S. 50. 1960 (1928) (l) a. thenyl methyl ether J J b. dithenyl other e. furfuryl thenyl ether The new compounds of this group were prepared as follows:

(1) Dithenyl ether. To a suspension of 1.32 g. (0.01 mole) of chloromethylthiophene [obtained by the method of F. F. BLICKE, J.A.C .S. 64, 477(1942)] and 1.2 g. (0.02 mole) of powdered potassium hydroxide in 10 ml. of ether there is added a solution of 3.5 g. (0.03 mole) of thenyl alcohol in 10 ml. of ether. The reaction mixture is stirred for l hour at room temperature, then refluxed for 30 minutes and finally allowed to stand over night. After filtration the ethereal solution is concentrated and the residue fractionally distilled. There is obtained 0.22 g. (10 percent) of dithenyl ether having a b.p. of 99C./0.01 mm. Hg. and a m.p. of 36.5. y

(l) c. Furfuryl thenyl ether is obtained by the same method as used for preparing compound (1) b., but using furfuryl alcohol instead of thenyl alcohol. The product thus obtained had a b.p. of 50C./0.01 mm. Hg.

Organoleptic evaluation data on representatives of this group of compounds are set out in TABLE X below.

X1 Thiazole Alcohols Compounds of this group have the following structural formula:

cu N

I cnoun methyl (4-methyl-thiazolyl-2) carbinol ethyl (4'methyl-thiazolyl-2) carbinol vinyl (4-methyl-thiazolyl-2) carbinol isobutyl (4-methyl-thiazolyl-2) carbinol The new compounds of this Group X can be prepared as follows:

(I) a. Methyl (4-methyl-thiazolyl-2) carbinol was preparedby starting from 4-methyl-thiazole and substituting the hydrogen atom in the 2-position by lithium by reaction ;with. butyllithium. The resulting metalorganic compound was reacted with acetaldehyde [cf. J.A.C.S. 74, 6260 (1952)]. The resulting product has a b.p. of l02-103C./9 mm. Hg.

(1)-b. Ethyl (4-methyl-thiazolyl 2) carbinol was prepared by'starting from 4-methylthia'z ole and substituting the hydrogen atom in the 2-po sition by lithium by reaction with butyllithium. The resulting metal-organic compound was reacted with propio'naldehyde [cf. J.A.C.S. 74, 6260 1952)]. The resulting product had a b.p. of l l-l lC./9 mm. Hg. and a m.p. of 67-72C.

-( 1) c. Vinyl (4-methyl-thiazolyl-2) carbinol was pre- 18 pared by starting from 4-methyl-thiazole and substituting the hydrogen atom in the 2-position by lithium by reaction with butyllithium. The resulting metal-organic compound was reacted with acrolein [cf. J.A.C.S. 74, 6260 (1952)]. The resulting product had a b.p. of 66C./0.005 mm. Hg.

(l) d. lsobutyl (4-methyl-2-thiazolyl) carbinol was prepared by starting from 4-methyl-thiazole and substituting the hydrogen atom in the 2-position by lithium by reaction with butyllithium. The resulting metalorganic compound was reacted with isovaleraldehyde [cf. J.A.C.S. 74, 6260 (1952)]. The resulting product had a b.p. of 94C./0.l mm. Hg.

Organoleptic evaluations are set out in TABLE XI below.

XII Pyridine Ethers and Alcohols Compounds of this group are found to have the following general formula;

wherein R is hydrogen or an alkoxy group, R is hydrogen or an alkyl group, and n is 0, l or 2. Examples of this group include:

2-( Z-hydroxyethyl )-pyridine 2-( 2 ethoxyethyl )pyridine (1) b. 2-Butoxy-pyridine was prepared according to the method described in J.A.C.S. 69, 1803 (1947) by condensing 0.17 mole of 2-bromo-pyridine with 0.195

' mole of sodium butoxide. By distillation of the reaction product there were obtained 15 g. of 2-butoxy-pyridine distilling at 78C./ 10 mm.Hg. n,, 1.4880; df 0.9723.

Organoleptic evaluations are set out in TABLE XII below.

XIII Pyrazine Ethers and Alcohols Compounds of this group are represented by the general formula:

v wherein R represents hydrogen or an alkyl group and n J.Org.Chem. 28, 1898 (1963) a. 2-hydroxymethyl-pyrazine b. 2-methoxymethylpyrazine c. Z-ethoxymethyl-pyrazine Compounds l) b. and l) c. were prepared by reacting 2-chloromethyl-pyrazine with the corresponding g, i sodium alkoxide according to the same method as used (a) 2 for the preparation of sulfides [cf. HOUBEN-WEYL, 5 3

4th edition, vol. 9, 97 (1955)]. The products thus obtained had the following boiling points:

compound (1) b.: 5lC./8 mm. Hg.;'

wherein R and R represent hydrogen or alkyl. compound (1) c.: 75C./8 mm. Hg.

Compounds in this group include for instance:

( l a. Thiophene-Z-aldehyde 0.11.

b. S-methyl-thiophene-Z-aldehyde Org.Syn. 36, 74 (1956) c. 3-methyl-lhiophene-Z-aldehyde *b.p. 8889C./l0 mm.Hg. d. -propyl.-thiophene-Z-aldehyde *b.p. 64-65C./0.002 mm.Hg. e. 5thenyl-thiophene-Z-aldehyde *m.p. 3l-32C.

* prepared according'to the same method as used for compound (1) c. (2) u. benzothiophene-Z-aldehyde .l.A.C.S. 74, 2935 (l952) b. Z-acetyLbenzothiophene Compt.Rend. 234, 736 (1952) Organoleptic evaluations are set out in TABLE Xlll Organoleptic evaluations are set out in TABLE XV below. below.

XlV Benzofuran Carbonyl Compounds XVI Pyrrole Aldehydes This group of compounds has the following general Compounds of this group have the structural formula formula:

(1) t j... cno

N l R wherein R is an alkyl, furfuryl or thenyl group.

Representative compounds include, for example:

wherein R and R may be hydrogen or alkyl.

(l) a. l-ethyl-pyrrole-2-aldehyde n.c.

b. l butyl-pyrrole-2-aldehyde Helv. l3, 349 (I930) c. l-butyl-pyrrole-3-aldehyde n.c. d. lamyl-py-rrole-2-aldehyde n.c. e. l-amyl-pyrrole-3-aldehyde n.c. f. l-a1methylbutyl-pyrrole-Z-aldehyde n.c. g. l-a-methylbutyl-pyrrole-3-aldehyde n.c. h. l-furfuryl pyrrole-2-aldehyde Helv. I3, 349 (I930) i. l-furfuryl-pyrrole-3-aldehyde n.c. j. l-thenyl-pyrrole-2-aldehyde n.c. k. l-isoamyl-pyrrole-Z-aldehyde Helv. I3, 349 (I930) Examples of compounds included in this definition The new compounds of this group XVl can be preare: 1 pared as follows:

(I) u. benzofuran-Z-aldehyde Bull. l962, I875 b. 2-acetyl-benzofuran J.A.C.S. 73, 754 (l95l) c. 7-methyl-benzofuran-Z-aldehyde n.c.

(l) c. 7-Methyl-benzofuran-2-aldehyde was prepared by formylating 7-methyl-benzofuran according to the same method as used for the preparation of benzoful) a. l-Ethyl-pyrrole-2-aldehyde was prepared from ran-2-aldehyde. The product thus obtained has the foll-ethyl-pyrrole [obtained by the method described in lowing ion peaks in its mass spectrum: 160 (100 per- Helv. 10, 387 (1927)] by introducing a formaldehyde cent), 159 (62 percent) and l3l (33 percent). group following the technique described in Org. Synth.

Organoleptic evaluations are set out in TABLE XIV 3' 6, 74 (1956). The product boiled at 73-75C./7 mm. below. Hg.

XV Thiophene Aldehydes (l) c. l Butyl pyrrole 3 aldehyde was prepared by Compounds of this group have the general formulae: bp' of l48l50C./1 l mm. Hg.

' (l) d. l-Amyl-pyrrole-2-aldehyde was prepared by (l) R i i the same method as used for compound (1) a. It has a hp of lll-ll2C./l1 mm. Hg.

CH0 (1) e. l-Amyl-pyrrole-3-aldehyde was prepared by the same method as used for compound (1) a. It has a wherein R is hydrogen, or an alkyl or thenyl group; and bp of l55l60C./l 1 mm.l-lg.

the same method as used for compound (1) a. It has a (l) f. 1-a-MethyIbutyl-pyrrole-2-aldehyde was prepared by the same method as used for compound 1) a. It has a b.p. of 103105C./l1 mm. Hg.

(1) g. 1-a-Methylbutyl-pyrrole-3-aldehyde was prepared by the same method as used for compound 1 a. It has a b.p. of 150C./11 mm. Hg.

1 h. I-Furfuryl-pyrrole-Z-aldehyde was prepared starting with l-furfuryl-pyrrole described by Reichstein in Helv. 15, 1450 (1932) as well as Gianturco et al. in Tetrahedron 20, 1763 1964). The aldehyde group was introduced by the Vilameyer reaction (e.g. by the method described in Bull. 1962, 1989). A small amount of the corresponding 3-aldehyde is obtained as a by-product and can be separated by fractional distillation. The Z-aIdehyde boils at 139140C./12 mm. Hg. and is a viscous colorless oil. The 3-aldehyde has a b.p. of 190C./12 mm. Hg.

(1) j. I-ThenyI-pyrrole-2 aldehyde was prepared by the same method as used for compound I h. It has a b.p. of 98C./().0O5 mm. Hg.

The organoleptic evaluations are shown in TABLE XVI below.

XVII Pyrazine Carbonyl Compounds Compounds of this group have the general formula:

N w rm-R wherein R is hydrogen or an alkyl group and n is 0 or 1. Examples of this group include:

C.A. 58.1(1180b(1963) J.A.C.S. 74. 3621 (I952) J.Org.Chcm. 23. 406 (I958) formylpyrazinc acetyl-pyrazine -acetonyl-pyrazine Organoleptic evaluations are tabulated in TABLE XVII below.

XVIII Aliphatic and Aromatic Ketones tion are follows:

(I I a. methyl amyl ketone c.a. h. methyl hexyl ketone 0.11. c. methyl heptyl ketone c.a. d. methyl octyl ketone c.a. e. methyl nonyl ketone ca.

22 -continued f. methyl decyl ketone ca g. methyl untlecyl ketone c.a. h. ethyl hutyl ketone 0.21. i. ethyl amyl ketone c.a.

5 j. dipropyl ketone c.a.

k. propyl isopropyl ketone J.A.C.S. 63. 3163 (I941 l. dLisopropyl ketone .I.A.C.S. 59. I826 1937) m. acetophentmc ca. n. propiophenone c.a. o. isopropyl phenyl ketone 0.21. p. methyl benzyl ketone ca 0' q. ethyl benzyl ketone c.a.

Organoleptic evaluations are tabulated in TABLE XVIII below.

XIX Furan Ketones This family of compounds have the following general formula:

(1) ll ll l 1 0 a Li 2 wherein n is 0. 1 or 2 and wherein R is hydrogen or methyl, and R is alkyl.

S-methyl-furfuryl) methyl ketone S-methyI-furfuryl) ethyl ketone k. 4furfuryl-2-butanone I. 4-(S-mcthylfuryl)-2-butanone rn. l(S-methylfuryl)-3-pentunone n.c. J.A.C.S. 72. 3695 (1950) Ber. 76. 192(1943) 40 The new compounds of this group can be prepared as follows:

(I) i. (S-Methyl-furfuryl) methyl ketone was prepared according to the procedure described by Hass et al. in J. Org. Chem. 15, 8 (1950) by condensing 5- methyl-furfuryI-aldehyde with nitroethane. The product has a b.p. of 75C./I0 mm. Hg.

(1) j. (S-MethyI-furfuryl) ethyl ketone was prepared by the same method as used for compound (I) i., except that I-nitropropane was used instead of nitroethane. The product has a b.p. of 97100C./l5 mm. Hg.

(1) m. l-(5-Methylfuryl)-3-pentanone was prepared by the method described in Ber. 76, 192 (1943). It has a b.p. of 101-102C./1 1 mm. Hg.

Organoleptic evaluation data are set out in TABLE XIX below.

XX Thiophene Ketones Compounds of this group which have been found to have utility in the concept of the instant invention have the following general formulae:

(2) l 1(011 Ucocu cu co S 2 n 3 3 wherein n is O or 1.

Representative compounds include:

wherein R,, R and R represent hydrogen or alkyl groups and R is an alkyl group,

Compounds which are representative of this group include:

. 1-furfuryl-2-acetyl-pyrrole n.c.

. l-thenyl2-acetyl-pyrrole J.A.C.S. 85. 2859 (1963) l-thenyl-3-acetyl-pyrrole J,A.C.S. 85, 2859 (1963) l-ucetyl-pyrrole Chem. & 1nd. 1965, 1426 l-propionyLpyrrole Ber. 89, 1938 (1956) 2'methyl-S-acetyl-pyrrole c.a.

. l,Z-dimethyl-Sacetyl-pyrrole n.c.

2,5-dimethyl-3-ucetyl-pyrrole Beilstein XXI, 277 (1935) l-methyl-3-acetyl-pyrrole n.c.

The new compounds included in this group can be prepared as follows:

Organoleptic evaluation data are set out in TABLE XX below.

XXI Pyrrole Ketones Compounds of this group have the general formulae:

wherein R is an alkyl group;

wherein R is hydrogen or an alkyl group and R is an alkyl group;

i d*" N l R l) a. l-Furfuryl-2-acetyl-pyrrole was prepared starting from l-furfuryl-pyrrole described by Reichstein in Helv. 15, 1450 (1932) as well as Gianturco et al. in Tetrahedron 20, 1763 1964). Acetylation by reaction of the Grignard intermediate with acetyl chloride [cf. Chem. Ber. 47, 1416 1914)] led to the desired ketone. (A small amount of the 3-isomer was also obtained, separable by fractional distillation). The product boils at 102C./0.03 mm Hg. and crystallizes on standing. Recrystallization from a mixture of methylene dichloride and petroleum ether gave a white crystalline product with a m.p. of 4243C.

(3) b. 1,2-Dimethyl-5 -acetyl-pyrrole was obtained by acetylating 1,2-dimethylpyrrole according to the method described in Ber. 47, 1416 (1914) [cf. also J.A.C.S. 85, 2859 (1963)]. The product has a. b.p. of 102106C./10 mm. Hg.

(4) b. 1-Methyl-3-acetyl-pyrrole was obtained as a by-product in the synthesis of I-methyI-Z-acetyI-pyrrole according to the method described in Ber. 47, 1416 (1914). The product has a b.p. of 132C./l2 mm. Hg.

Evaluation data are set out in TABLE XXI below.

XXII Thiazole Carbonyl Compounds Compounds of this group have the following general wherein R and R are hydrogen or alkyl groups. Representative compounds of this group are:

(l) a. 4-methyl-2-acetyl-thiazole Bull. 20, 702 (1953) b. 4methyl2-propionyl-thiazole n.c. c. S-methyl-Z-acetyl-thiazole Bull. 20, 702 (1953) d. 4-methyl-2-butyryl-thiazole n.c. e. 4-methyI-Z-formyl-thiazole n.c.

' The new compounds included in this group can be prepared as follows:

(l) b. 4-Methy1-2-propiony1-thiazo1e was prepared according to the method described in Bull. 20, 702 (1953)by reacting 4-methy1-thiazole with ethyl-magnesium bromide and acylating the obtained Grignard intermediate with propionyl chloride. The product has a b.p. of 83-88C./9 mm. Hg.

(1) d. 4-Methyl-2-butyry1thiazo1e was prepared by the same method as compound (1) b, but using butyric anhydride as the acylating agent. The product has a b.p. of ll 115C./8 mm.

(1) e. 4-Methyl-2-formyl thiazo1e wasprepared by oxidizing Z-hydrdxymethyl-4-methy1-thiazole with chromic acid in a sulfuric acid medium according to the method described in J.A.C.S. 53, 1470 (1931). The product was identified by mass spectrometry (peaks M/e and relative intensity): 71 (100 percent), 127 (97 percent) and 72 (48 percent).

Organoleptic evaluation data are set out in TABLE XXII below.

XXIII Pyridine Carbonyl Compounds Compounds of this group have the general formula:

(1) n (cn ii n wherein R represents hydrogen, an alkyl group or a phenyl group, R represents hydrogen, an alkyl group or an acyl group and n is O, l or 2. v

Representative compounds include:

.-benzoy1-pyridine I. 2,6-diacety1-pyridine -(7-Pyridyl)-butan-2-one The new compound, 4-('y-pyridy1)-butan-2-one, was prepared as follows:

8 ml. of 2-n NaOH solution were added to a mixture of 10.8 g. (0.1 mole) of pyridine-4-aldehyde, 100 ml. of

water and 10 m1. of acetone at 1215C. After a reaction time of 3 minutes the reaction mixture was neutra l ized with 10 percent aqueous acetic acid, saturated :with NaCl and extracted with ether. After removal of 26 the ether the residue was distilled. There were obtained 8.4 g. of 4-(7-pyridy1)-3-buten-2-one as a yellow oil of b.p. l35-l38C./0.07 Torr. 5.24 g; of this product were dissolved in 30 ml. of ethanol and hydrogenated in the presence of 4 g. of Ni-catalyst. Distillation of the reaction product yielded 4-('y-pyridy1)-butan-2-one of b.p. 8385C./0.05 Torr; n, 1.047; u 1.516.

Organoleptic evaluation data are set out in TABLE XXIII below.

XXIV Alpha-Diketones Compounds of this group which have been found to have utility in the concept of this invention are of the formulae CH3COCOR C2H ,COCOR wherein R is an alkyl group or a phenyl group.

Compounds representative of this group include:

J.Chem.Soc. 1946, 56

Ber. 22, 2121(1889) Ber. 22, 2122 (1889) J.pr.Ch.[2] 58, 402 (1898) n,, 1.4214, d 0.9183 c.a. (British Drug House) a. acetylbutyryl b. acetylisobutyryl c. acetylisovalerianyl d. acetylcaproyl e. acetylbenzoyl f. S-methyl-heptanedione-2,3 n.c. g. 5-methyl-octanedione-2,3 n.c. h. acetylvalerianyl n.c.

i. acetylheptanoyl n.c. a. dipropionyl Bull.[3], 31, 629,650 (1906) b. heptaneJA-dione Bu1l.[3], 31, 1174 (1904) c. S-methy1-heptane-3,4-dione n.c.; prepared by the method in Bull.[3], 31, 1145 (1904); b.p. 55C./l2 mm.Hg.

. and 15 ml. of water were added to the distillation residue. The distillation was then continued at a bath temperature of 180C. After 15 ml. of distillate consisting of the reaction product and water had been collected, the flask was again cooled, and the addition of water followed by distillation were repeated several times until the reaction product was completely distilled. The combined distillates were extracted with ether. after washing the extract with aqueous sodium carbonate and water and evaporation of the solvent, the residue was distilled. There were obtained 3.9 g. of pure 5-methyl-heptan-2,3-dione distilling at 45-47C./8 Torr. n 1.4200; df 0.9099.

(1) g. 5-Methyl-octan-2,3-dione was prepared according to the same method as 5-methy1-heptan-2,3- dione, except that 0.5 mole of acetol, 0.55 mole of amethyl-pentenal and 4.5 ml. of cono. HCI were used for the reaction. There were obtained 16 g. of pure 5- methyl-octan-2,3-dione distilling at 6566C./ 11 Torr; n 1.4258; df 0.9107.

(1) h. Acetylvalerianyl was prepared according to the same method as compound (1) f. It has a b.p. of 71-72C./44 mm. Hg.

(1) i. Acetylheptanoyl was prepared by hydrolyzing 3-oximino-nonan-2-one according to the method of Bouveault et al. described in Bu1l.Soc.Chim. France [3}31, 1145 (1904). 3-Oximino-nonan-2-one'was obtained by nitrosation of nonan-2-one with ethyl nitrite according to the method described in Org.React. VII,

XXV Thiophene Alpha-diketones Compounds of this group have the following general formula:

1 l Lemma wherein R is hydrogen or a methyl group and wherein R is an alkyl group.

Representative compounds include:

b.p. of 74C./9

(I) a. l-(thienyl-2)-propane-1,2-dione n.c b. l-(3-methyl-thienyl-2)-propane-l ,Z-dione n.c c. l-(S-methyl-thienyl-Z)-propane-1,2 dione n.c d. l-(thienyl-2)-butan-l,2-dione n.c

Thenew compounds included in this group can be obtained as follows:

(1) a. 1-(Thienyl-2 )-propane-1,2-dione was prepared by acylating thiophene according to the method described in J.A.C.S. 72, 3695 (1950), subjecting the resulting 2-propionylthiophene to the action of nitrosyl chloride and hydrolyzing the reaction product in formic acid solution with nitrosyl sulfuric acid as described in Bull. [3131, 1 163 (1904). The product formed bright yellow crystals and melted at 48-50C.

(l) b. l-(3-methyl-thienyl-2)-propane-l,2-dione was prepared by acylating thiophene according to the method described in J.A.C.S. 72, 3695 (1950), subjecting the resulting 3-methyl- 2-propionyl-thiophene to the action of nitrosyl chloride and hydrolizing the reaction product in formic acid solution with nitrosyl sulfuric acid as described in Bull. {3]31, 1163 (1904). The product had a b.p. of 93C./11 mm. Hg.

(1) c. l-(5-Methyl-thienyl-2)-propane-1,2-dione was prepared by the same method as compound (1) a. It has a b.p. of l50l60C. (bath temp.)/l1 mm. Hg.

. furfuryl propionate furfuryl butyrate furfuryl isobutyrate furfuryl isovalerate furfuryl crotonate furfuryl tiglate furfuryl alphamethylbutyrale furfuryl B,B-dimethylacrylate furfuryl valerate ethyl furoate propyl furoate isopropyl furoate butyl furoate isobutyl furoate isoamyl furoate methyl 3-(nz-furyl)-propionate ethyl 3-(a-furyl)-propionate The organoleptic evaluations gave the results set out in TABLE XXV below.

XXVI Pyrrole Alpha-diketones This group of compounds has the general formula:

U CO OFl wherein R is hydrogen or alkyl and R is alkyl.

Representative compounds of this group include e.g.:

ILC.

ILC.

(l) a. (pyrrolyl-2)-propan-1,2-dione b. (pyrrolyl-2)-butan1,Z-dione XXVII Furan Esters Compounds of this group have the general formulae:

. 0 l l u CHZ-O-C-R 0 wherein R is an alkyl group comprising at least 2 carbon atoms; and

wherein R is an alkyl or alkenyl group.

Representative compounds of this group include:

(cH coo *The Furans, page 226 *The Furans", page 226 *The Furans", page 226 n.c. *The Furans", page 36 n.c. *The Furans", page 513 *The Furans", page 513 *The Furans", page 513 *The Furans", page 513 *The Furans", page 513 *The Furans", page 513 C.A. 32, 53977 (1938) 'Thc Furans", Reinhold Publishing Company. New York (1953).

(1) c. 1-(Thienyl-2)-butan-1,2-dione was prepared The new compounds included in this group can be from 2-butyryl-thiophene via the oxime according to obtained by reacting the corresponding acid chlorides the method used in the furan series and described in Tetrahedron 20, 2959 (1964). The product has a b.p. of -l23C. (bath temperature) 11 mm. Hg.

with furfuryl alcohol, e.g. according to the method described in Houben-Weyl, 4th ed., Vol. 8, 543 (1952). There are thus obtained:

(l) d. Furfuryl isovalerate, b.p. 97-98C./ll mm. Hg. (1) e. Furfuryl crotonate, b.p. 96-98C./ll mm. Hg.

(1) g. Furfuryl oz-methylbutyrate, b.p. 96C./ll mm. Hg.

(1) h. Furfuryl ll3-ll5C./ll mm. Hg.

(1) i. Furfuryl valerate, b.p. 100l04C./11 mm. Hg.

In the organoleptic evaluation tests these compounds gave the results set out in TABLE XXVll below.

XXVlll Thiophene Esters Compounds of this group have the following general formulae:

ll ll m wherein R is alkyl or furfuryl; and

B,B'-dimethylacrylate, b.p.

wherein R is hydrogen or alkyl.

Representative compounds of this group include:

( l a. methyl thiophene-2-carboxylate c. propyl thiophene-Z-Carboxylatc d. butyl thiophene-Z-carboxylate e. isoamyl thiophene-Z-carboxylate n.c. f. furfuryl thiophene-Z-carboxylate n.c. (2) a. thenyl formate n.c. b. thenyl acetate n.c.

The new compounds included in sub-class (l) of this group can be obtained by reacting thionyl chloride with the corresponding alkoxides according to the method described in J.A.C.S. 77, 6709 (1955). There were thus obtained:

1 e. lsoamyl thiophene-Z-carboxylate, b.p. 7980C./O.3 mm. Hg.

( 1 f. Furfuryl thiophene-Z-carboxylate, b.p.

XXlX Pyridine Esters Compounds of this group are of the general formula 1) (CH COOR wherein R stands for lower alkyl and n is or 1.

Representative compounds of this group include:

l a. methyl (pyridyl-2)-acetate c.a. b. methyl (pyridyl3)-acetate c.a. 0. methyl (pyridyl-4)-acetate ca d. ethyl (pyridyl-2)-acetate c.a. e. ethyl (pyridyl-3)-acetate ca f. ethyl (pyridyl-4)-acetate c.a.

Organoleptic evaluataion data are set out in TABLE XXIX below.

XXX Aromatic Sulfur Compounds Compounds of this group are of the general formulae:

J.A.C.S. 77, 6709 (I955) b, ethyl lhiophene-2-carboxylale J.A.C.S. 77, 6709 (1955) J.A.C.S. 77, 6709 (1955) J.A.C.S. 77. 6709 (1955) wherein R stands for hydrogen, hydroxy, alkoxy or alkyl and R represents hydrogen or alkyl;

wherein R stands for hydrogen, hydroxy, alkyl or alkoxy, R may be hydrogen or alkyl, R represents alkyl or benzyl and n is 0, l or 2; and

wherein R stands for alkyl or phenyl. Representative compounds include:

(I) a. 2-methoxy benzenethiol Ber. 39, 1348 (1906) b. benzenethiol c.a. 2-hydroxy-thiophenol Beilstein 6, 793

d. Lmethyl-benzenethiol c.a.

e. S-methyl-benzenethiol c.a.

f. 4-methyl-benzenethiol c.a.

g. 2,4-dimethyl-benzenethiol Ber. 32, H47

h. 3,4-dimethyl-benzenethiol J.Org.Chem. 26, 4047 (I961) i. ethyl-benzenethiol Ber. 59, 349

2. j. Z-ethoxy-benzenethiol .l.pr.Ch. H4, 231, 235

-contmued 4-methoxy-benzenethiol mcthyl phenyl sulfide dibenzyl sulfide phenyl methyl disulfide diphenyl disulfide c.a. J.Chem.Soc. l922, 1404 J.A.C.S. 85, 1618 (1963) Ber. 56, 1929 (1923) (CH -S H wherein R stands for hydrogen or alkyl, R represents 5 hydrogen, alkyl, furfuryl or alkyl-substituted phenyl, and It stands for 0, l or 2, with the provision that, if R is hydrogen and n is 1, R is neither methyl or furfuryl;

O (5) l! an wherein R is alkyl or furfuryl;

0 R H 1 K-' cu-a-a-R wherein R represents hydrogen or alkyl and R stands 40 for alkyl or furfuryl; and

wherein R represents an alkyl or an acyl group.

Representative compounds in this group include:

acetic chloride or anhydride with furfurylmercaptan according to the method described in Houben-Weyl, 4th ed., vol. 9, 753 (1955). The product has a b.p. of 92C./l2 mm. Hg.

According to the same method, but starting from the corresponding acid chloride or anhydride, the following products were obtained:

(1) b. Furfurylthiol propionate, b.p. 97C./ 10

mm. Hg.

(1) c. Furfurylthiol butyrate, b.p. lO5.5106.5/1O mm. Hg.

(1) d. Furfurylthiol furoate, b.p. l10C./0.0l mm. Hg.

(1) e. Furfurylthiol [3,B-dimethylacrylate, b.p.

85C./0.0l5 mm. Hg.

(1) f. Furfurylthiol tiglate, b.p. 84.587.5C./0.03 mm. Hg.

(1) g. Furfurylthiol formate was prepared according to the method used for the synthesis of furfuryl formate and described in J.A.C.S. 64, 1583 (1942). The product had a b.p. of 7778C./8 mm. Hg.

(1) h. 2-(Furyl-2)-ethanthiol acetate was prepared by reacting thioacetic acid with 2-vinyl-furane under the action of UV light and in the presence of benzoyl peroxide according to the method described in J .Org.- Chem. 27, 2853 (1962). The thio-ester, after isolation by distillation had a b.p. of lO0103C./0.05 mm. Hg.

(2) a. S-Methylfurfuryl methyl sulfide was prepared by reacting 5-methylfurfuryl-mercaptan with dimethyl sulfate in alkaline solution according to known methods. S-Methylfurfurylmercaptan was obtained from the corresponding alcohol by the method described in Org.Syn. 35, 67 (1955). The product is a colorless liquid boiling at 7l-72C./11 mm. Hg.

(2) b. Furfuryl propyl sulfide was prepared by reacting sodium furfurylmercaptide with n-propyl bromide according to the method described in Houben-Weyl, 4th ed., vol. 9, 97 (1955). The product has a b.p. of 9lC./15 mm. Hg.

(2) c. Furfuryl isopropyl sulfide was prepared by the same method as used for compound (2) b., except that isopropyl bromide was used instead of n-propyl bro- (I a. furfurylthiol acetate n.c. b. furfurylthiol propionate n.c. c. furfurylthiol butyrate n.c. d. furfurylthiol furoate n.c. e. furfurylthiol B,B-dimethylacrylate n.c. f. furfurylthiol tiglate n.c. g. furfurylthiol formate n.c. h. 2-(furyl-2)-ethanthiol acetate n.c. (2) a. S-methylfurfuryl methyl sulfide n.c. b. furfuryl propyl sulfide n.c. c. furfuryl isopropyl sulfide n.c. d. furfuryl S-methylfuryl sulfide n.c. e. S-methylfuryl methyl sulfide n.c. f. 2-(furyl-2)-ethanthiol n.c (3) a. methylthiol furoate n.c. (4) a. difurfuryl disulfide .I.A.C.S. 52, 214l (1930) (5) a. (benzofuryl-2)-methyl methyl sulfide n.c. b. (benzofuryl-Z)-methylthiol acetate n.c.

The new compounds included in this group XXXI can be obtained as follows:

(l) a. Furfurylthiol acetate was prepared by reacting mide. The product has a b.p. of 84C./l6 mm. Hg.

(2) d. Furfuryl S-methylfuryl sulfide was prepared according to the method used for the synthesis of al- 33 kylthio-furans and described in C.A. 59, 8681d 1963). Z-Methylfuran was reacted with butyl-lithium and then with sulfur. The resulting thiol was further reacted (without prior isolation) with furfuryl chloride. The product was a slightly yellowish oil having a b.p. of 67C./0.04-0.05 mm. Hg.

(2) e. Methyl S-methylfuryl sulfide was prepared by the same method as used for compound (2) d. The product was a light yellow liquid having a b.p. of 80C./45-50 mm. Hg.

(2) f. 2-(Furyl-2)-ethanethiol was prepared by saponifying 24 g. of 2-furylethanethiol acetate with alkali in aqueous-alcoholic medium. After refluxing for 90 minutes the reaction mixture was neutralized with acetic acid and then extracted with ether. Upon distillation there were obtained 14.4 g. of 2-(furyl-2)-ethanethiol having a b.p. of 6162C./0.03 nim. Hg; n 1.5653 df 1.153 I (3) a. Methylthiol fuorate was prepared by reacting furoyl chloride with methylmercaptan according to the method described in Houbenweyl, 4th ed., vol. 9, 753 (1955). It has a b.p. of 92-93C./11 mm. Hg-

(5) a. Benzofurfuryl-Z methyl sulfide was prepared by reacting (benzofurfuryl-2')-mercaptan with dimethyl sulfate in alkaline solution. The sulfide thus obtained has a b.p. of lO8-lO9C./O.4 mm. Hg.

l The starting (benzofurfuryl-Z)-mercaptan was obtained from the corresponding alcohol according to the methoddescribed in Org. Synth. 35, 67 (19.55).

(5) b. (Benzofurfuryl-D'thiol acetate, was prepared by the same method as used for compound 1) a. (furfurylthiol acetate). The 1 product has. a b.p. of l2Q- -122C. /0.8 mm. Hg.

.Evaluation .test data are set out low.

,"XXXII Thiophene Sulfur Compounds i [Long air in TAnLaxxxi bewherein R represents hydrogen, and n is 1 or 2; and

r Lii-sn alkyl, acetyl or thenyl,

(l) a. thenyl-mercaptan b. thenyl methyl sulfide c. thenyl thiol acetate d. 2-(thienyl-2)-ethanethiol e. 2-(thienyl-2)-ethanethiol-acetate n.c.

(2) al thiothenoic acid S-methyl ester n.c. b. thiothenoic acid S-ethyl ester n.c.

c. thiothenoic acid S-furfuryl ester The new compounds of thisgroup can be obtained as follows:

CompLrend: 229, Compt.rend. 229,

' to the method described in J.Org.Chem. 27, 2853 (1962), and the resulting addition product was sub- 10 jected to hydrolysis with an acid. The product has a b.p.

of C./O.1 mm. Hg.

('1) e. 2-(Thienyl-2)-ethanethiol acetate was obtained as the intermediate product obtained by reacting 2-vinyl-thiophene with thioacetic acid in the prepara- 'tion' of compound (l) d. above. The product has a b.p.

of C./0.07 mm. Hg.

(1) f. Dithenyl sulfide was prepared by the same method as used for compound (1) b; (dithenyl ether) of Group X above, except that thenylmercaptan was used instead of thenyl alcohol. The product has a b.p. of 118C./0.04 mm. Hg.

Compounds (2) a, (2) b, and (2) c, were prepared by reacting thionyl chloride with the sodium salts of the corresponding mercaptans in alcoholic solution according to the method described in .l.C.A.S. 77, 6709 (1955). After refluxing for 1 hour the reaction mixture was filtered and concentrated. The residue was purified by chromatography on a silica-gel column using 'a'benz'ene-hexane mixture 8:2as the eluant. The structure of the resulting products was identified by mass spectrometry:

(2) a. Thiothenoic acid S-methyl ester: lon peaks with relative intensities: 1 1 1 percent), 39 (22 percent) and 158 (12 percent).

(2) b. Thiothenoic acid S-ethyl ester: lon peaks with relative intensities: 111 (100 percent), 39 (17 percent) and 172 (10 percent).

" (2) c. Thiothenoic acid S-furfuryl ester: Ion peaks with relative intensities: 111 (100 percent), 81 (73.5

percent) and 39 (20 percent). Organoleptic evaluation data are set out in TABLE XXXII below.

' XXXIII Pyridine Sulfur Compounds The compounds included in this group have the general formula:

N (cH SR (pyridyl-2)-methanthiol b. 2mercapto-pyridine As examples there can be mentioned:

, C.A. 55. 4542b (1961) -continued k. 2-(pyridyl-2)-ethyl furfuryl sulfide l. (pyridyl-2)-methyl methyl sulfide m. (pyridyl-2)-methyl ethyl sulfide n. (pyridyl-2)-methanethiol acetate The method used for preparing the known compound (1) h. [2-(pyridyl-2)-ethyl methyl sulfide] was as follows: 2-Vinylpyridine was reacted with methylmercaptan by the action of UV light in the presence of trace amounts of benzoyl peroxide and diphenyl sulfide. The product has a b.p. of 48C./0.03 mm. Hg.

The same method was used for preparing the known compound l j., except that thioacetic acid was used instead of methylmercaptan. The product has a b.p. of 80C./0.02 mm. Hg.

The new compounds included in this Group XXXIII can be obtained as follows:

(l) c. Z-Methylthio-pyridine was prepared according to the method described in Houben-Weyl, 4th ed., vol. 9, 7 (1955) by alkylating 2-mercapto-pyridine with methyl halide. The resulting pyridinium salt was neutralized with NaOH and the base thus obtained extracted and distilled. The product had a b.p. of 67-68C./l0 mm. Hg.

l d. 2-Ethylthio-pyridine was prepared by the same method as used for compound (1) c., except that ethyl halide was used instead of methyl halide. The product had a b.p. of 7777.5C./8 mm. Hg. (1) e. (Pyridyl-2)- thiol acetate was prepared by reacting acetic anhydride with 2-mercaptopyridine in alkaline medium according to the method described in Houben-Weyl, 4th ed., vol. 9, 753 (1955) and in J.A.C.S. 59, 1089 (1937). The product has a b.p. of l17l l8C./9 mm. Hg.

(1) i. 2-(Pyridyl-2)-ethyl ethyl sulfide was prepared by the same method as used for compound (1) h., except that ethylmercaptan was used instead of methylmercaptan. The product'has a b.p. of 62C./0.005 mm. Hg.

(1) m. (Pyridyl-2 )-methyl ethyl sulfide was prepared by the same method as used for compound (1) l. The product has a b.p. of lO7-110C./1O mm. Hg.

1) n. (Pyridyl-2)-methanethiol acetate was prepared by reacting acetyl chloride with 2-mercaptomethylpyridine in alkaline medium. The product has a b.p. of 102-103C./9 mm. Hg.

Evaluation test data are reported in TABLE XXXlll below.

XXXlV Pyrrole Sulfur Compounds These sulfur compounds correspond to the following general formula:

TLC.

TLC.

Helv. 47. I754 (1964) wherein R represents alkyl, furfuryl or acyl. As examples, there can be mentioned:

(1) a. N-methyl-pyrryl-2 methyl sulfide n.c. b. N-methyI'pyrryI-Z ethyl sulfide n.c. c. N-methyl-pyrryl-Z furfuryl sulfide n.c. dv (N-methyl-pyrryl-Z)-methylthiol acetate n.c.

The new compounds included in this Group XXXIV can be obtained as follows:

(1 a. N-Methyl-pyrryl-2 methyl sulfide was prepared by alkylating of N-methyl-(pyrryl-Z )-methylmercaptan with methyl iodide according to the method described in Houben-Weyl, 4th ed., vol. 9, 97 1955 The product has a b.p. of C./1O mm. Hg.

(1) b. N-Methyl-pyrryl-Z ethyl sulfide was prepared by the same method as used for compound (1) a., except that ethyl bromide was used in place of methyl iodide. The product has a b.p. of 99C./ 10 mm. Hg.

(1) c. N-Methyl-pyrryl-2 furfuryl sulfide was prepared by the same method as used for compound (1) a., except that furfuryl chloride was used in place of methyl iodide. The product has a b.p. of 94C./0.0l mm. Hg.

(1) d. (N-Methyl-pyrryl-2)-methylthiol acetate was prepared by acylating (N-methyl-pyrryl-2)-methylmercaptan according to the method described in Houben- Weyl, 4th ed., vol. 9, 753 (1958). The product has a b.p. of 69C./0.05 mm. Hg.

Evaluation test data are set out in TABLE XXXlV below.

XXXV Pyrazine Sulfur Compounds The compounds of this group can be represented by the following general formulae:

CH 5' R wherein R stands for hydrogen, alkyl, furfuryl or acyl. Illustrative examples of compounds corresponding to formulae (1) and (2) include:

a. (2-methylpyrazinyl-3. -5 and -6) furfuryl sulfide b. pyrazinylmethyl-mercaptan ILC.

TLC.

-cont1nued c. pyrazinylmethyl methyl sulfide d. pyrazinylmethyl ethyl sulfide e. pyrazinylmethyl furfuryl sulfide f. pyrazinylmethylrhiol acetate g. Z-pyrazinyl-ethyl mercaptan h. 2-pyrazinyl-ethyl methyl sulfide i. 2-pyrazinyl-ethyl ethyl sulfide 2'pyrazinyl-ethyl furfuryl sulfide Z-pyrazinyl-ethylthiol acetate 2,5-dimethyl-3-mercapto-pyrazine 2,S-dimethylG-methylthio-pyrazine 2,5-dimethyl-3-ethylthio-pyrazine 2,5Dimethyl-3-acetylthiopyrazine 2,5-dimethyl-3-furfurylthio-pyrazine The new compounds included in this group can b obtained as follows: i

(1) a. (2-Methylpyrazinyl-3, -5 and -6) furfuryl sulfide (mixture): A mixture of 2-methyl-3-, 5- and 6- chloropyrazine was prepared by chlorination of 2- methylpyrazine according to the method described in J. Org. Chem. 26, 2356, 2360 (1961). 0.2 Mole of the above 2-methyl-chloropyrazine mixture was added to 0.2 mole of a sodium furfurylmercaptide suspension in 250 ml. of xylene. The mixture was boiled for 6 hours. After cooling 250 ml. of water were added, the organic layer was concentrated and distilled. 13.5 g. of a mixture of (2-methylpyrazinyl-3, -5 and -6) furfuryl sulfide were obtained; b.p. 153156C./10 Torr; u 1.5970; d 1.2164.

(1) b. Pyrazinylmethylmercaptan: a solution of 6.3 g. (0.05 mole) of chloromethylpyrazine [obtained according to the method described in J. Org. Chem. 26, 2356 (1961 in 20 ml. of ether was added slowly, with stirring, to a solution of sodium hydrogensulfide (60 percent) in 50 ml. of absolute methanol. Stirring of the reaction mixture at room temperature was continued for 3 hours. The precipitate which had formed was removed by filtering, the solvents were evaporated, and the residue was dissolved in water. The solution was extracted twice with ether. The aqueous phase was neutralized with acetic acid and extracted with ether. After drying of the extract the solvent was evaporated and the residue distilled. 0.25 g. of pyrazinylmethylmercaptan boiling at 4445C./0.07 mm. Hg. was obtained.

(1) c. Pyrazinylmethyl methyl sulfide was prepared according to the method described in Houben-Weyl, 4th ed., vol. 9, 97 (1955) by reacting chloromethylpyrazine [obtained by the method described in J. Org. Chem. 26, 2356 (1961)] with sodium methylmercaptide. The product has a b.p. of 105-106C./l2 mm. H

%l) d. Pyrazinylmethyl ethyl sulfide was prepared by the same method as used for compound (1) c., except that sodium ethylmercaptide was used in place of sodium methylmercaptide. The product has a b.p. of l14116C./12 mm. Hg.

(1) e. Pyrazinylmethyl furfuryl sulfide was prepared by the same method as used for compound (1) 0., except that sodium furfurylmercaptide was used instead of sodium methylmercaptide. The product has a b.p. of ll6C./0.05 mm. Hg.

(1) f. Pyrazinylmethylthiol acetate was prepared by acetylation of pyrazinylmethylthiol according to the method described in Houben-Weyl, 4th. ed., vol. 9, 753 (1955). The product has a b.p. of 52C./0.02 mm. Hg.

(1) g. 2-Pyrazinyl-ethyl mercaptan was prepared by reacting vinylpyrazine [obtained by the method described in J. Org. Chem. 27, 1363 (1962)] and hydrolizing the resulting thiolic acid ester according to the TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

TLC.

method described in J. Org. Chem. 22, 980 (1957). The product has a b.p. of 56.560C./0.003 mm. Hg.

(1) h. 2-Pyrazinyl-ethyl methyl sulfide was prepared by reacting vinylpyrazine [c.f. J. Org. Chem-2 7, 1363 (1962] with methylmercaptan by the action of ultra vi.- olet light and in the presence of benzoyl peroxide by the method described in Acta Chem. Scand. 8, 295 (1954). The product was identified by mass spectrometry. It has a b.p. of 5769C. at 0.05 mm. Hg.

(1) i. 2-Pyrazinyl-ethyl ethyl sulfide was prepared by the method used for compound (1) h., but using ethylmercaptan. It has a b.p. of C./0.03 mm. Hg.

(1) j. 2-Pyrazinyl-ethyl furfuryl sulfide was prepared by the method used for compound 1) h., but using furfuralmercaptan. The product has a b.p. of 116l17C./0.01 mm. Hg.

(1) k. Z-Pyrazinyl-ethylthiol acetate was prepared by reacting vinylpyrazine with thioacetic acid in the presence of benzoyl peroxide as a catalyst according to the method described in J. Org. Chem. 27, 2853 (1962). The product has a b.p. of C./0.02 mm. Hg.

(2) a. 2,3-Dimethyl-3-mercapto-pyrazine: A solution of 1.3 g. (0.023 mole) of sodium hydrogensulfide and 2.5 g. (0.01 mole) of 2,5-dimethyl-3-iodo-pyrazine in 70 ml. of absolute methanol was refluxed for 3 hours. After evaporation of the alcohol the residue was dissolved in l-n NaOH, the solution was filtered and the filtrate was neutralized with acetic acid. After isolation by the usual treatments the reaction product was sublimated. There was obtained 0.81 g. of a yellow powder having a m.p. of 182185C.

(2) b. 2,5-Dimethyl-3-methylthio-pyrazine 2.85 g. (0.02 mole) of 2,S-dimethyl-3-chloropyrazine and 0.06 mole of methylmercaptan were dissolved in a solution of 0.7 g. of sodium in 20 ml. of absolute ethanol. The reaction mixture was refluxed for 45 minutes. After removal of the alcohol by distillation the residue was dissolved in water and the sulfide was extracted with ether and distilled. The product (yield 75.6 percent) has a b.p. of 40-50C./11 mm. Hg.

(2) c. 2,5-Dimethyl-3-ethylthio-pyrazine was prepared in the same manner as compound (2) b., except that 0.06 mole of ethylmercaptan was used instead of methylmercaptan. The product (yield 75 percent) has a b.p. of l28C./9 mm. Hg.

(2) d. 2,5-Dimethyl-3-furfurylthio-pyrazine was prepared in the same manner as compound (2) b., except that 0.06 mole of furfurylmercaptan was used instead of methylmercaptan. The product (yield 75 percent) has a b.p. of -120C./0.02 mm. Hg.

(2) e. 2,5-Dimethyl-3-acetylthio-pyrazine was prepared by acetylating 2,5 -dimethyl-3-mercapto-pyrazine [compound (2) a.] with acetic anhydride in an alkaline medium according to the method described in Houben- Weyl, 4th ed., vol. 9, 753 (1955). The product has a 

1. AS A NEW COMPOSITION OF MATTER A SOLUBLE COFFEE MATERIAL HAVING ADDED THERETO A MINOR, BUT FLAVOUR MODIFYING AMOUNT OF A COMPOUND SELECTED FROM THE GROUP OF COMPOUNDS HAVING THE GENERAL FORMULA:
 2. The soluble coffee of claim 1 wherein the added compound is diphenyl.
 3. The soluble coffee of claim 1 wherein the added compound is 2-methyl-diphenyl.
 4. The soluble coffee of claim 1 wherein the added compound is 3-methyl-diphenyl.
 5. The soluble coffee of claim 1 wherein the added compound is 4-methyl-diphenyl.
 6. The soluble coffee of Claim 1 wherein the added compound is 4, 4''-dimethyl-diphenyl.
 7. A process for the alteration of the natural flavor of soluble coffee material which comprises adding thereto a minor, but flavor-modifying amount of a compound selected from the group of compounds having the general formula:
 8. The process of claim 7 wherein the added compound is diphenyl.
 9. The process of claim 7 wherein the added compound is 2-methyl-diphenyl.
 10. The process of claim 7 wherein the added compound is 3-methyl-diphenyl.
 11. The process of claim 7 wherein the added compound is 4-methyl-diphenyl.
 12. The process of claim 7 wherein the added compound is 4,4''-dimethyl-diphenyl.
 13. A composition selected from the group consisting of foodstuffs and beverages to which has been added an effective flavor improving amount of a compound selected from the group of compounds having the general formula:
 14. The composition of claim 13 wherein the added compound is diphenyl.
 15. The composition of claim 13 wherein the added compound is 2-methyl-diphenyl.
 16. The composition of claim 13 wherein the added compound is 3-methyl-diphenyl.
 17. The composition of claim 13 wherein the added compound is 4-methyl-diphenyl.
 18. The composition of claim 13 wherein the added compound is 4, 4'' dimethyl-diphenyl.
 19. A process for the alteration of the flavor of a composition selected from the group consisting of foodstuffs and beverages which comprises adding thereto a minor, but flavor-modifying amount of a compound selected from those represented by the general formula:
 20. The process of claim 19 wherein the added compound is diphenyl.
 21. The process of claim 19 wherein the added compound is 2-methyl-diphenyl.
 22. The process of claim 19 wherein the added compound is 3-methyl-diphenyl.
 23. The process of claim 19 wherein the added compound is 4-methyl-diphenyl.
 24. The process of claim 19 wherein the added compound is 4, 4'' dimethyl-diphenyl. 